The UNC-CH Center for Genomics and Society focuses on newly emerging ethical, legal and social implications (ELSI) of genomics research as the field matures and shifts its focus from small efforts to those on a much larger scale. These gene discovery and disclosure activities involve large numbers of individuals from whom DNA has been collected, studies with a small number of individuals whose whole DNA sequences are being examined, and the creation of complex data sets that may be linked in a variety of ways to multiple other sources of data. DNA collected in these activities may test a population for the presence of a known genetic disorder, use genotypic data to develop guides for drug dosing, combine genotype and phenotype data for large-scale prospective studies, collect and store DNA and environmental data in genetic registries, or consolidate DNA collected by multiple investigators to create a bank for use in current or future exploratory studies. We argue that although large-scale gene discovery and disclosure efforts have tremendous scientific promise and the potential to lead more directly to changes in public policy or clinical practice, they also raise a wide range of ELSI issues not apparent in smaller-scale efforts. (1) Scaling up may change the implications of genetic information for individuals, families, or populations, particularly when genetic findings are ascribed to individuals by virtue of their membership in socially defined groups. (2) Large-scale genomic research may alter challenges to informed consent in response to shifting estimations of risk and benefit. (3) New technologies and data collection and storage capacities may pose unique ELSI issues as investigators, subjects and relevant institutions grapple with regulation of the use of DNA samples, control of data, and their dissemination. (4) All of these concerns are also integral to understanding the most efficient and judicious translation of genomic research findings into clinical or public health practice. We have assembled an interdisciplinary team of investigators to conduct a research on these ELSI issues raised by large scale genomics; offer a research ethics consultation service for genomic researchers; facilitate policy initiatives that are informed by our research findings; and provide training, education, and outreach particularly focused on underrepresented minorities, to foster continued ELSI research on large-scale genomics. In addition to our goal of addressing public health priorities in newborn screening and in the translation of other genetic technologies, inclusion of underrepresented minorities in all aspects of our Center activities highlights the importance of consultation from populations with greatest interest in and most affected by large-scale genomic studies intended to address health disparities.